Advertisement

Effects of Gluten Intake on Risk of Celiac Disease: A Case-Control Study on a Swedish Birth Cohort

Published:October 07, 2015DOI:https://doi.org/10.1016/j.cgh.2015.09.030

      Background & Aims

      Early nutrition may affect the risk of celiac disease. We investigated whether amount of gluten in diet until 2 years of age increases risk for celiac disease.

      Methods

      We performed a 1-to-3 nested case-control study of 146 cases, resulting in 436 case-control pairs matched for sex, birth year, and HLA genotype generated from Swedish children at genetic risk for celiac disease. Newborns were annually screened for tissue transglutaminase autoantibodies (tTGA). If tested tTGA positive, time point of seroconversion was determined from frozen serum samples taken every 3 months. Celiac disease was confirmed by intestinal biopsies. Gluten intake was calculated from 3-day food records collected at ages 9, 12, 18 and 24 months. Odds ratios (OR) were calculated through conditional logistic regression.

      Results

      Breastfeeding duration (median, 32 wk) and age at first introduction to gluten (median, 22 wk) did not differ between cases and tTGA-negative controls. At the visit before tTGA seroconversion, cases reported a larger intake of gluten than controls (OR, 1.28; 95% confidence interval [CI], 1.13–1.46; P = .0002). More cases than controls were found in the upper third tertile (ie, >5.0 g/d) before they tested positive for tTGA seroconversion than controls (OR, 2.65; 95% CI, 1.70–4.13; P < .0001). This finding was similar in children homozygous for DR3-DQ2 (OR, 3.19; 95% CI, 1.61–6.30; P = .001), heterozygous for DR3-DQ2 (OR, 2.24; 95% CI, 1.08-4.62; P = .030), and for children not carrying DR3-DQ2 (OR, 2.43; 95% CI, 0.90–6.54; P = .079).

      Conclusions

      The amount of gluten consumed until 2 years of age increases the risk of celiac disease at least 2-fold in genetically susceptible children. These findings may be taken into account for future infant feeding recommendations.

      Keywords

      Abbreviations used in this paper:

      CD (celiac disease), TEDDY (The Environmental Determinants of Diabetes in the Young), tTGA (tissue transglutaminase autoantibodies)
      To read this article in full you will need to make a payment
      AGA Member Login
      Login with your AGA username and password.

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ludvigsson J.F.
        • Green P.H.
        Clinical management of coeliac disease.
        J Intern Med. 2011; 269: 560-571
        • Catassi C.
        • Gatti S.
        • Fasano A.
        The new epidemiology of celiac disease.
        J Pediatr Gastroenterol Nutr. 2014; 59: S7-S9
        • Sollid L.M.
        • Thorsby E.
        HLA susceptibility genes in celiac disease: genetic mapping and role in pathogenesis.
        Gastroenterology. 1993; 105: 910-922
        • Hunt K.A.
        • Zhernakova A.
        • Turner G.
        • et al.
        Newly identified genetic risk variants for celiac disease related to the immune response.
        Nat Genet. 2008; 40: 395-402
        • Ivarsson A.
        • Persson L.A.
        • Nyström L.
        • et al.
        Epidemic of coeliac disease in Swedish children.
        Acta Paediatr. 2000; 89: 165-171
        • Ivarsson A.
        • Myléus A.
        • Norström F.
        • et al.
        Prevalence of childhood celiac disease and changes in infant feeding.
        Pediatrics. 2013; 131: e687-e694
        • Stördal K.
        • White R.A.
        • Eggesbö M.
        Early feeding and risk of celiac disease in a prospective birth cohort.
        Pediatrics. 2013; 132: e1202-e1209
        • Aronsson C.A.
        • Lee H.
        • Liu E.
        • et al.
        Age at gluten introduction and risk for celiac disease.
        Pediatrics. 2015; 135: 239-245
        • Vriezinga S.M.
        • Auricchio R.
        • Bravi E.
        • et al.
        Randomized feeding intervention in infants at high risk for celiac disease.
        N Engl J Med. 2014; 371: 1304-1315
        • Lionetti E.
        • Castellaneta S.
        • Francavilla R.
        • et al.
        Introduction of gluten, HLA status and the risk of celiac disease in children.
        N Engl J Med. 2014; 371: 1295-1303
        • Ivarsson A.
        • Hernell O.
        • Stenlund H.
        • et al.
        Breast-feeding protects against celiac disease.
        Am J Clin Nutr. 2002; 75: 914-921
        • TEDDY Study group
        The Environmental determinants of Diabetes in The Young (TEDDY) study: study design.
        Pediatr Diabetes. 2007; 8: 286-298
        • Liu E.
        • Lee H.
        • Aronsson C.A.
        • et al.
        HLA Haplotype and country and the risk of celiac disease in early childhood.
        N Engl J Med. 2014; 371: 42-49
        • Weile B.
        • Cavell B.
        • Nivenius K.
        • et al.
        Striking differences in the incidence of childhood celiac disease between Denmark and Sweden: a plausible explanation.
        J Pediatr Gastroenterol Nutr. 1995; 21: 64-68
        • TEDDY Study group
        The Environmental Determinants of Diabetes in The Young (TEDDY) study.
        Ann N Y Acad Sci. 2008; 1150: 1-13
        • Hagopian W.A.
        • Erlich H.
        • Lernmark Å.
        • et al.
        The Environmental Determinants of Diabetes in The Young (TEDDY): genetic criteria and international diabetes risk screening of 410 000 infants.
        Pediatr Diabetes. 2011; 12: 733-743
        • Vehik K.
        • Fiske S.W.
        • Logan C.D.
        • et al.
        Methods, quality control and specimen management in an international multi-center investigation of type 1 diabetes: TEDDY.
        Diabetes Metab Res Rev. 2013; 29: 557-567
        • Yang J.
        • Lynch K.F.
        • Uusitalo U.
        • et al.
        Factors associated with longitudinal food record compliance in a paediatric cohort study.
        Public Health Nutr. 2015; 19: 1-10
        • Koskinen O.
        • Villanen M.
        • Korponay-Szabo I.
        • et al.
        Oats do not induce systemic or mucosal autoantibody response in children with coeliac disease.
        J Pediatr Gastroenterol Nutr. 2009; 48: 559-565
        • Uusitalo U.
        • Kronberg-Kippilä C.
        • Andren Aronsson C.
        • et al.
        Food composition database harmonization for between-country comparisons of nutrient data in the TEDDY study.
        J Food Compost Anal. 2011; 24: 494-505
      1. National Food Agency, Uppsala, Sweden. The Swedish Food Composition Database. Available: http://www.slv.se/en-gb/Group1/Food-and-Nutrition/The-Food-Database/. Assessed: November 20, 2014.

        • van Overbeek F.M.
        • Uil-Dieterman I.G.
        • Mol I.W.
        • et al.
        The daily gluten intake in relatives of patients with coeliac disease compared with that of the general Dutch population.
        Eur J Gastroenterol Hepatol. 1997; 9: 1097-1099
        • Arentz-Hansen H.
        • McAdam S.N.
        • Molberg Ö.
        • et al.
        Celiac lesion T cells recognize epitopes that cluster in regions of gliadines rich in proline residues.
        Gastroenterology. 2002; 123: 803-809
        • Mearin M.L.
        • Biemond I.
        • Peña A.S.
        • et al.
        HLA-DR phenotypes in Spanish coeliac children: their contribution to the understanding of the genetics of the disease.
        Gut. 1983; 24: 532-537
        • Tjon J.
        • van Bergen J.
        • Koning F.
        Celiac disease: how complicated can it get?.
        Immunogenetics. 2010; 62: 641-651
        • Vader W.
        • Stepniak D.
        • Kooy Y.
        • et al.
        The HLA-DQ2 gene dose effect in celiac disease is directly related to the magnitude and breadth of gluten-specific T cell responses.
        Proc Natl Acad Sci U S A. 2003; 100: 12390-12395
        • Andrén Aronsson C.
        • Uusitalo U.
        • Vehik K.
        • et al.
        Age at first introduction to complementary foods is associated with sociodemographic factors in children with increased genetic risk of developing type 1 diabetes.
        Matern Child Nutr. 2015; 11: 803-814
        • Ascher H.
        • Holm K.
        • Kristiansson B.
        • et al.
        Different features of coeliac disease in two neighbouring countries.
        Arc Dis Child. 1993; 69: 375-380
        • Almquist-Tangen G.
        • Dahlgren J.
        • Rosvall J.
        • et al.
        Milk cereal drink increases BMI risk at 12 and 18 months, but formula does not.
        Acta Paediatr. 2013; 102: 1174-1179